Photochemically treated fresh frozen plasma for transfusion of patients with acquired coagulopathy of liver disease
An ex vivo photochemical treatment (PCT) process was developed to inactivate pathogens in fresh frozen plasma (PCT-FFP). A prospective, controlled, double-blinded, randomized study was conducted to evaluate the efficacy and safety of PCT-FFP compared with conventional FFP (C-FFP). Patients (n = 121) with acquired coagulopathy, largely due to liver disease, including hepatic transplantation, were transfused with either PCT-FFP or C-FFP for up to 7 days. Primary end points were changes in the prothrombin time (PT) and the partial thromboplastin time (PTT) in response to the first FFP transfusion. Secondary analyses compared changes in the PT and the PTT, factor VII levels, clinical hemostasis, blood component usage, and safety following FFP transfusions for up to 7 days. Following the first transfusion, correction in the PT and PTT adjusted for FFP dose and patient weight was not different. Changes in the PT were equivalent between treatment groups (P = . 002 by noninferiority). Equivalence was not demonstrated for changes in the PTT. Following multiple transfusions, correction of the PT and the PTT was similar between groups. No differences were observed in use of blood components, clinical hemostasis, or safety. These results suggest PCT-FFP supported hemostasis in the treatment of acquired coagulopathy similarly to conventional FFP.
A randomized, controlled Phase III trial of therapeutic plasma exchange with fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light compared to untreated FFP in thrombotic thrombocytopenic purpura
BACKGROUND Photochemical treatment of fresh-frozen plasma (FFP) with amotosalen and ultraviolet (UV) A light (PCT FFP) results in inactivation of a broad spectrum of pathogens while retaining coagulation factor activity, antithrombotic proteins, and von Willebrand factor-cleaving protease (VWF-CP) activity. STUDY DESIGN AND METHODS A randomized, controlled, double-blind Phase III trial was conducted with PCT FFP or control FFP for therapeutic plasma exchange (TPE) in patients with thrombotic thrombocytopenic purpura (TTP). Owing to the rarity of this diagnosis, the trial was not powered to demonstrate small differences between treatment groups. Patients were treated with study FFP for a maximum of 35 days until remission was achieved (for a maximum of 30 daily study TPEs with no remission) plus an additional 5 days after remission. RESULTS Among the 35 patients treated, the primary endpoint, remission within 30 days, was achieved by 14 of 17 (82%) PCT patients and 16 of 18 (89%) control patients (p = 0. 658) The 90 percent confidence interval for treatment difference in remission rate for test - control was (-0. 291 to 0. 163). Time to remission, relapse rates, time to relapse, total volume and number of FFP units exchanged, and number of study TPEs were not significantly different between groups. Improvement in VWF-CP and inhibitors was similar for both groups. The overall safety profile of PCT FFP was similar to control FFP. No antibodies to amotosalen neoantigens were detected. CONCLUSION The comparable results between treatment groups observed from this small trial suggest that TPE with PCT FFP was safe and effective for treatment of TTP.
Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients
BACKGROUND A randomized, double-blind trial is reported of the clinical efficacy of red blood cells (RBCs) treated for pathogen inactivation with S-303, a synthetic labile alkylating agent. STUDY DESIGN AND METHODS Patients undergoing complex cardiac surgeries were randomly assigned to receive either S-303-treated (test) or conventional (control) RBC transfusion during surgery and for 6 days thereafter. Efficacy was evaluated by comparing the occurrence of a composite primary endpoint of treatment-related morbidity (myocardial infarction and renal failure) and mortality. RESULTS Two-hundred twenty-three patients were randomly assigned and 148 patients who received transfusions (74 with S-303-treated RBCs and 74 with control RBCs) were evaluable. The incidence of the primary endpoint was equivalent between the two groups (22 and 21% in the S-303-treated and control RBC groups, respectively). Secondary endpoints, including hemoglobin increment (mean, 1. 4 vs. 1. 5 g/dL), number of RBC transfusions (mean, 4. 4 vs. 3. 8 units), and other blood product support, were also comparable. The adverse event profile was similar between groups; however, patients who received S-303 RBCs were significantly more likely to develop constipation and less likely to suffer supraventricular extrasystoles. Four patients (2 test and 2 control) demonstrated positive indirect antiglobulin tests with reactivity for S-303 RBCs at one or more time points before or after transfusion, without evidence of hemolysis. CONCLUSION S-303-treated and conventional RBCs were equivalent with respect to clinical efficacy and safety in supporting the transfusion needs of cardiac surgery patients. Investigations are under way to ascertain the significance of S-303 RBC antibodies and to prevent their occurrence.
Autologous fibrin sealant reduces pain after tonsillectomy
OBJECTIVES/HYPOTHESIS Pain is a major cause of morbidity after tonsillectomy. Although various efforts have been made to reduce pain, the use of oral analgesics, which can have adverse side effects, remains the standard of care. It is hypothesized that fibrin sealant, used to achieve hemostasis and enhance healing in many surgical procedures, might help decrease pain after this operation. STUDY DESIGN A prospective, randomized, blinded study was performed on 20 children aged 5 to 17 years who were undergoing tonsillectomy, to evaluate the efficacy of FIBRIN SEALANT in reducing postoperative pain. METHODS All patients pre-donated 40 mL of blood from which autologous concentrated fibrinogen was prepared by cryoprecipitation. In the fibrin sealant group, fibrinogen and topical bovine thrombin were sprayed onto the surgical site to form fibrin sealant at the conclusion of tonsillectomy. The 10 patients in the control group (C) received no fibrin sealant. Patients rated their level of pain immediately after surgery and at regular intervals for 3 days after surgery using the Wong-Baker Faces Pain Rating Scale (1-6). Emesis, postoperative bleeding, medications, and adverse events were also evaluated. RESULTS At 7.00 P.M. on postoperative day (POD) 0, the mean +/- SD fibrin sealant group pain score (2.9+/-0.41 units) was significantly lower than for the C group (4.1+/-0.43 units; P < or = .05). There was also a trend in favor of less pain in the fibrin sealant group at 7:00 P.M. on POD 1, with a mean of 3.5+/-0.43 units versus 2.4+/-0.48 units for C (P = .15). The odds of a patient in C experiencing emesis were 8.16 times higher, (P < or = .05) than for patients in the fibrin sealant group. CONCLUSIONS Fibrin sealant significantly reduced pain the evening after pediatric tonsillectomy and also decreased the chance of experiencing emesis. Thus fibrin sealant may be clinically useful as an adjunct to tonsillectomy.